DESCRIPTION: (APPLICANT'S ABSTRACT) The reinforcing efficacy of a stimulus is malleable and is determined in large part by the environmental context in which the stimulus is encountered. One way in which the reinforcing efficacy of a stimulus can be altered is by associating the stimulus with another stimulus that is high in reinforcing efficacy. For example, a tone has no intrinsic reinforcing efficacy to a rat and will not serve to maintain long-term responding. However, if the tone has been paired with the repeated delivery of morphine to the rat it will acquire reinforcing efficacy and serve to maintain responding. Historically, this process has been called conditioned reinforcement and the previously neutral tone would be called a conditioned reinforcer. Drugs of abuse are typically high in their reinforcing efficacy. However, the natural environment in which humans self-administer drugs contains other sources of reinforcement which likely become associated with the drug. The purpose of this application is to investigate whether the pairing of a drug with other sources of reinforcement can augment the reinforcing efficacy of the drug for humans. Previous work has suggested that, in animals, drugs can acquire additional reinforcing efficacy by associating their ingestion with other sources of reinforcement (e.g., Grant and Sampson, 1985). The issue has not been systematically investigated in humans. In an important study Johanson, Mattox, and Schuster (1995), established a paradigm for investigating the role of conditioned reinforcement in drug self-administration. In this study volunteers selected between two differently colored placebo capsules, one of which was associated with a high magnitude of monetary reinforcement and the other of which was associated with a low magnitude of monetary reinforcement. Participants preferred the capsule that was associated with the high magnitude of monetary reinforcement. This study demonstrated that placebo capsules could acquire incentive-motivational properties on the basis of their association with other sources of reinforcement. The studies proposed in this application will utilize the Johanson et al. (1995) paradigm to investigate whether the reinforcing efficacy of drugs (d-amphetamine and diazepam) can be altered through the process of conditioned reinforcement.